Hypericin is one of the chemical constituents from a perennial herbaceous plant, Hypericum perforatum or St. John's Wort. Hypericum is known to have medicinal properties since ancient times and it is widely used in phytotheraphy. Hypericum has been widely researched for its antidepressant and anti-viral properties. In addition to these properties, Hypericum has historically been used for a variety of neurological conditions, including anxiety, insomnia due to restlessness, irritability, neuralgia, trigeminal neuralgia, neuroses, migraine headaches, fibrositis, dyspepsia, and sciatica. Hypericum contains several compounds of biological interest, including naphthodianthrones, e.g. hypericin and pseudohypericin, phloroglucinols, e.g. hyperforin and ashyperforin, and a broad spectrum of flavonoids which are considered to be primarily responsible for Hypericum's activity. However, the lack of a clearly definable pharmacologic mechanism of Hypericum and its chemical components cause the failure of identifying the constituents most responsible for Hypericum's activity.
Clinical studies demonstrated that Hypericum is effective in treating mild depression. Animal studies also showed that Hypericum extract relieved depressant symptoms. It was reported that Hypericum extract resulted in a down-regulation of adrenergic receptors in the rat frontal cortex after subchronic treatment. Some reported that hypericin inhibited monoamine oxidase (MAO) activity in vitro, but others have failed to confirm this effect. Other proposed mechanisms involve effects on serotonin. At very high doses, Hypericum extract inhibited seretonin re-uptake although it is not known which chemical in the extract is responsible. Studies have shown that both hypericin and pseudohypericin inhibited a variety of virus. Hypericin has been reported to inhibit the growth of glioma cell lines in vitro and to be a potent inducer of glioma cell death due to inhibition of protein kinase C(PKC). Receptortyrosine kinase activity of epidermal growth factor has also been reported to be inhibited by hypericin. These later effects have been linked to both the antiviral and antineoplastic activity.
It is known (F. R. Buhler, J. Hypertension supplement 15(5):s3–7, 1997; B. Cremers et al., J. Cardiovascular Pharmacology, vol. 29(5), pp. 692–6, 1997) that T-type channels are involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. It was reported that Mibefradil, a selective T-channel blocker, induces peripheral and coranary vasodilation. There is no reflex sympathetic activation and no negative inotropic effect. It increases coronary blood flow without increasing oxygen consumption and causes a slight slowing of the heart rate, thereby inducing diastolic relaxation. The latter improves subendocardial and small artery perfusion. Ventricular ectopic activity is reduced with mibefradil. The renin-angiotensin-aldosterone system and endothelin effects are blunted by T-channel inhibition. It is believed that mibefradil could lead to a greater therapeutic index and greater safety over conventional non-selective or L-type calcium channel blockers in the treatment of cardiovascular diseases. Mibefradil has been used to treat hypertension and angina clinically. It was reported that Zonisamide, a antiepileptic drug reduces T-type calcium current (M. Kito et al., Seizure, vol. 5(2), pp. 115–9, 1996). T-type calcium channels also facilitate insulin secretion by enhancing the general excitability of these cells. Therefore, T-type calcium channels may be therapeutic targets in hypo- and hyperinsulinemia (A. Bhaftacharjee et al., Endocrinology, vol. 138(9), pp. 3735–40, 1997). A direct link between T-type calcium channel activity and steroidogenesis has been suggested (M. F. Rossier et al., 1996).